This proposal deals with in depth investigation on the mechanisms responsible for pulmonary injury, pulmonary ischemia-reperfusion and specifically in orthotopic lung transplants in rats. The principal investigator has amassed an impressive body of preliminary data to support his hypothesis that reduced endothelial nitric oxide coupled with enhanced exppression of endothelial cell adhesion molecules are major factors in lung graft failure and pulmonary reperfusion injury. There are three specific aims. Specific Aim 1 is to evaluate the role of the cAMP and cGMP pathways in maintaining pulmonary integrity. Specific Aim 2 is to evaluate the role of neutrophil recruitment and particularly the actions of P-selectin expression on the vascular endothelium. Specific Aim 3 is to determine optimal conditions for lung preservation and particularly to develop an improved preservation solution which preserves the vascular endothelium so that transplants can be successful.